Malaria

One Nurse At A Time modules are intended to help nurses understand disease processes that are uncommon in our work practices at home. They are intended to be practical guides and not exhaustive dissertations. Education is a dynamic, ongoing process. We value your input and comments on the content of this module. Please feel free to write to OneNurseAtATime@gmail.com.

MALARIA

Once you read the story “T Girl” (first published in Nurses Beyond Borders), you know malaria can kill. A simple mosquito bite leads to a potentially deadly cascade of parasites in the human body. Every year nearly one million people die of malaria, mostly in the developing world. 225 million people are infected annually according to the World Health Organization (WHO). 225 million T Girls.

Wherever you work in Africa, Latin America or Asia, you should be alert for symptoms of malaria for your patients and also for you. This module will discuss signs and symptoms of malaria, treatment and prevention. The protocols we offer are internationally recognized and supported by WHO and the Centers for Disease Control and Prevention (CDC). As a nurse working in malaria-prone areas, chances are you will be called upon to care for malaria-infected patients.

THE DISEASE

“Malaria” refers a disease caused by one of four major species of Plasmodium parasite: P. falciparum, P. vivax, P. ovale and P. malariae. P. falciparum is the version that can cause severe malaria attacks and death. The others are generally less severe, but can cause death in young children, the elderly and persons who are immuno-compromised. Billions of dollars are spent annually on research for prevention and cure, but malaria has not been halted as a major killer in the developing world.

The vector is the female anopheles mosquito (Only the female feeds on blood; the male feeds on plant nectar). She is a larger-sized mosquito with a right angle proboscis. (picture?) Normally she bites between dusk and dawn (she’s a night biter). She first must bite an infected person thereby ingesting the malaria parasite herself. On her subsequent bites, she injects the parasites into her host during her blood meal. The parasites infest the human liver, where they multiply and find their way into the red blood cells in the circulation. Inside the red blood cells, P. falciparum multiplies rapidly, rupturing the cell and spewing parasites into the blood stream causing cyclical fever spikes. The infected red blood cells stick to the walls of the microcirculation, disrupting blood flow to the placenta, kidneys, retinas and brain. Patients typically become symptomatic about 2 weeks after the inoculating bite.

Malaria cannot be “caught” from another person or animal. However, the parasite can be found in banked blood for over 2 weeks, so transfusion is a potential mode of transmission (persons should be screened prior to donation). Possible, but rare, is direct person to person transmission via bloody needle stick. There is no mother to child transmission during childbirth, and malaria is not sexually transmitted.

P. falciparum is the dominant presentation in sub Saharan Africa, although P. vivax is present in some areas and is common in India and Central America. Medical treatment varies according to the species of malaria parasite, so check the WHO and CDC websites (www.WHO.org and www.CDC.gov) before you depart for your mission, and take the appropriate protocol with you. In some areas, malaria is prevalent year round. More commonly, it dramatically increases during the rainy season when mosquitoes breed and multiply.

Symptoms can mimic those of other tropical febrile illnesses such as Relapsing Fever, Kala Azar, Typhoid, Typhus and Dengue. As you research the area you’re travelling to, also look for the presence of these diseases to help with your differential diagnosis.

High fever up to 104F or 40C. Fever from P. falciparum infection can be nearly continuous or more commonly cyclical, spiking every 36 – 48 hours. The fever is frequently associated with shaking chills and sweating.

Diarrhea, nausea and vomiting. Dehydration can occur from severe diarrhea.

Change in level of consciousness, posturing, agitation, delirium. May be from high fever or sequestration of parasites in the brain leading to cerebral malaria.

Seizures (don’t mistake for febrile seizures which are infrequent and short in duration)

Enlarged liver and spleen, abdominal pain. If you’ve never felt a spleen or liver, you will in malaria endemic areas!

Acute renal failure and hematuria when hemoglobin from lysed red blood cells leaks into the urine, called “Blackwater Fever” (If you watched the movie “Out of Africa”, there was a character who died of Blackwater Fever).

Hypoglycemia in children

Anemia (from lysed red blood cells and liver/spleen involvement)

Pregnant women have higher risk contracting P. falciparum malaria, perhaps because of the sequestration of parasites in the placenta. Maternal malaria increases the risk of low birth weight babies, stillbirths and infant mortality.

Subsequent attacks tend to be less severe over time.

DIAGNOSIS

The presence of the malaria parasite can distract the practitioner from considering other causes of fever and shock. Be sure to exhaust all potential sources of infection before diagnosing “only malaria.” Malaria cannot be diagnosed by symptoms alone because often times the symptoms resemble those of other febrile illnesses. Presumptive treatment with anti-malarial drugs without confirmation of parasites has led to worldwide drug resistance. The 2010 WHO guidelines call for a confirmatory test prior to starting treatment. A laboratory exam of a blood slide is only relevant if it’s accurate and results can be produced within a couple hours to aid the clinician in treatment. Good quality labs are not found throughout the developing world and are labor intensive in the face of outbreaks.

Field Rapid Diagnostic Tests (sometimes referred to as RDT) can be quickly and accurately used for large numbers of patients. They take approximately one drop of blood and 15 minutes. Rapid tests can either exclusively determine the presence of P. falciparum (such as Paracheck) or a combined test can differentiate P. falciparum from other species of Plasmodium. The combined test is only used in locations where multiple species are found.

Rapid tests are not used to screen for malaria, they are used to confirm clinically suspected malaria. However, screening is done on blood donors, pregnant women in antenatal visits, and on admission to nutrition programs. As good as rapid tests are, they cannot be 100% accurate and there is always the possibility of human error.

If the patient is clinically suspected of uncomplicated malaria but the rapid test is negative, do not treat with anti-malarials.

If the patient is clinically suspected of severe malaria but the rapid test is negative, consider bacterial infections as sources of fever and consider antibiotics and consider treating with artemisinin based drugs (treatment protocols discussed below).

If no testing is available but the patient is symptomatic and it’s an endemic area, treat patients with artemisinin based drugs.

It is important to note that rapid tests may be negative in the presence of a low parasite load (for example, in persons from outside the endemic area). Paracheck will remain positive even after the infection has been appropriately treated (the antigen remains elevated for at least a month), so it is not helpful to repeat the test to evaluate efficacy of treatment.

During an outbreak where more than 80% of symptomatic patients test positive and testing is too difficult for the numbers of patients being seen, it is acceptable to give anti-malarials without a test for clinically suspicious cases.

UNCOMPLICATED vs. SEVERE MALARIA vs. CEREBRAL MALARIA

Uncomplicated malaria is defined as fever and

Headache

Chills and shivering

Abdominal pain

Body ache

Decreased appetite

Splenomegaly

Joint pain

Diarrhea/nausea/vomiting

This patient can eat and drink and although sick, is not mentally altered. Patient can be treated as an outpatient with oral artemisinin derivatives.

Severe malaria is defined as fever and

Altered level of consciousness

Anemia – blood transfusions should be available

Seizures

Jaundice

Shortness of breath or tachypnea

Severe malnutrition

Unable to eat or drink

Dark urine or anuria

This patient is severely ill with altered mental status. Patient must be admitted for IV or IM artemisinin drugs and close observation.

Cerebral malaria describes severe and life threatening encephalopathy featuring unarousable coma. Left untreated, cerebral malaria is fatal in 24 – 72 hours. This patient is critically ill and must be admitted for IV or IM artemisinin drugs.

TREATMENT FOR P. FALCIPARUM MALARIA

Chloroquine can be used to treat P. Falciparum only in Central America, Haiti and Dominican Republic. It is resistant in all other areas of the world and should not be used. Quinine (pronounced “key-neen” in many countries) has been long used for malaria but has been mostly replaced by a more effective class of drug.

Current treatment for P. falciparum malaria is based on artemisinin, an herb used in China for thousands of years to treat fever. Artemisinin clears the malaria parasite from the blood rapidly, and is always used in combination with a partner drug to slow drug resistance. Artemisinin comes in three forms:

Oral: ACT or Artemisinin Combination Therapy. Patients who are awake and alert enough to swallow are treated with ACT. An artemisinin derivative (Artesunate, artemether or dihydroartemisinin) is combined with another drug (amodiaquine, Fansidar, Mefloquine and others) based on efficacy in that area as indicated in the national protocol. If the effectiveness of partner drugs is unknown, a combination of artemether and lumefantrine (CoArtemether or CoArtem brand) is used.

The first dose should be given under observation at the time of your consultation. ACT comes in a 6 tab, color-coded blister pack based on age/weight. It’s taken twice daily for three days with food. ACT should not be used in the first trimester of pregnancy. If it’s the only available treatment, evaluate the risks and benefits in a newly pregnant patient – there have been no safety studies during the first trimester. ACT can be given safely in the second and third trimesters and is safe for breastfeeding mothers.

Artemether – an oil-based, injectable artemisinin drug, appropriate only for IM use. Peaks in 10 hours on average. DO NOT GIVE IV.

Artemether dose is 3.2 mg/kg IM once on Day 1, plus 1.6 mg/kg once daily until patient is able to swallow. Once able to take PO, switch to ACT twice daily for 3 days.

Artesunate – a water-based, injectable artemisinin drug, appropriate for IV or IM administration. WHO recommends Artesunate IV for first line treatment of severe malaria in adults and is currently rewriting protocols (to be published in 2011) to include IV Artesunate as first line treatment of severe malaria in children. IV is the preferred route, but in areas where IV administration is not possible (inadequate equipment, supplies or trained staff), IM is acceptable. IM Artesunate is clinically superior to IM Artemether. However, Artesunate comes in a powder that must be mixed as opposed to Artemether which is ready to draw up from a glass ampule. Peak is at 20 minutes on average.

Hypothetically, Artesunate can be given in rectal suppository form. Unless you have a refrigerator (not common in rural African countries), suppositories melt and are unusable.

Artesunate dose is 2.4 mg/kg at 0, 12 and 24 hours, then every 24 hours until the patient is able to take oral meds. Then switch to ACT twice daily for 3 days.

Quinine can be used as an alternative if artemisinin drugs are not available. It is complicated to administer, has harsher side effects and can rapidly reach toxic levels. It can cause permanent blindness, seizures, cardio-toxicity and coma. Quinine should be administered IV over 4 hours. It must be mixed and administered by skilled professionals for accurate dosing, infusion and monitoring for side effects. Quinine should be avoided IM – it can cause sterile abscesses and is quite painful (the largest abscess I have ever seen was from injecting quinine in the hip).

The main use for Quinine IV is for women with severe malaria in their first trimester.

Also may use ibuprofen in children over 3 months 30 mg/kg per day in 3 divided doses. Ibuprofen in children should be used only for fever control and short term (a few days rather than weeks) to avoid kidney concerns. Adult dose: 400 – 600 mg three times daily.

You will have to investigate country protocols (www.WHO.org and www.CDC.gov) for what types of malaria are present in the area you’ll be working. For example, if you’re in an area with P. vivax in addition to P. falciparum, don’t use the Artesunate/suphadoxine-pyrimethamine combination (AS/SP). SP (Fansidar) won’t be effective against P. vivax, even though it’s effective against P. falciparum.

P. vivax is the second most common species of malaria and is the dominant malaria outside of the African continent. It is considered “benign malaria” because fatality rates are much lower than with P. falciparum. But symptoms can be significant with high fevers, pain and weakness. Don’t dismiss P. vivax malaria infections – treat appropriately and aggressively.

P. vivax and P. ovale form dormant parasite stages called hypnozoites in the liver which can reactivate and cause relapses weeks, months and even years later. Once the parasite has been eliminated from the bloodstream with Chloroquine, the remaining hypnozoites must be removed from the liver with Primaquine or there is a high risk of relapse.

P. vivax and P. ovale treatment: Oral Chloroquine for 3 days unless there is reported resistance. Dose : Day 1 and Day 2 give 10 mg of base/kg once daily. Day 3 give 5 mg base/kg once daily. Follow with a 2 week course of Primaquine 15mg daily for 14 days – this is called a “radical cure” because it eliminates the parasites from the blood and hypnozoites from the liver. Primaquine should not be given during lactation.

PREVENTION

VECTOR CONTROL: The anopheles is a rapidly mutating mosquito that is able to adapt to its changing environment, causing the failure of many eradication approaches. Environmental laws dictate which chemicals can be used in various countries. Although the use of DDT eliminated malaria from the US, it was banned in the 1970s for its negative side effects on humans.

IRS or Indoor Residual Spraying. Chemicals are sprayed onto the interior walls of homes, killing mosquitoes that stop and stand on the wall after feeding. Unfortunately, mosquitoes can become resistant to a pesticide relatively quickly. Only WHOPES (World Health Organization Pesticide Evaluation Scheme) approved chemicals should be used.

It’s important to drain standing stagnant water – this is where the anopheles mosquito breeds. Unfortunately, mosquitoes also breed in the slow moving water at riversides (where people wash clothing, bathe, swim and collect water).

Scientists are actively researching creating sterile or genetically engineered malaria-resistant mosquitoes which would breed with local populations and stop their ability to reproduce.

BITE PREVENTION

ITN Insecticide Treated Nets. Only WHOPES (World Health Organization Pesticide Evaluation Scheme) approved bed nets should be used. Nets are made of tightly woven mesh fibers impregnated with insecticide that won’t wash out. There has been a huge effort to distribute these bed nets in endemic areas, with an estimated 80% current coverage. However, nets have a 3 year lifespan and many are now in need of replacement. Nets are typically hung from the ceiling and draped over the bed. Picture of my bed with net somewhere However, in many developing countries, people do not sleep on raised beds but rather on the ground or on mats. Obviously, the individual is only protected when covered by the net while in bed and not during the period of dusk (around 6 pm in sub Saharan Africa) to bedtime when the female anopheles also bites.

DEET – If travelling in endemic areas, it is important to bring/buy topical mosquito spray or lotion and be vigilant about applying it before dusk.

CHEMICAL PROPHYLAXIS

Vaccine – many are in development but so far none are available

Antimalarial meds do not give 100% protection, but should prevent severe attacks. Drugs: oral mefloquine (don’t take in first trimester of pregnancy), malarone, doxycycline (don’t take at any time during pregnancy). Travellers should take prophylactic medications. But they are not practical on a large scale basis because populations in endemic areas don’t have access to meds and can’t afford a lifetime supply. People in endemic areas may develop resistance to certain strains of malaria after repeated infections.

For travellers, the most commonly used prophylactic medications are:

Mefloquine or Larium. Start taking one tablet per week one week prior to potential exposure and continue for 4 weeks after leaving the endemic area. Mefloquine has frequent side effects of neurological and psychological problems. “Mild” side effects may be sleep disturbances, vivid dreams or nightmares. “Significant” side effects can be depression, hallucinations and outright psychotic behavior.

Doxycycline taken daily is cheap and easy to obtain anywhere in the world. Doxy must be taken on an empty stomach, and sun exposure can cause burns or staining of the skin.

Malarone taken daily has fewer side effects, but is expensive. Start 2 days before exposure and for 7 days after exiting the endemic area.

CONCLUSION

When I travel to malaria endemic areas, I take mefloquine religiously. Even so, on my second mission in Africa I got malaria: three days of unrelenting body-wracking pain, weakness, high fever, shaking chills and hallucinations. I had to drag myself 50 yards across the sand to squat over the outdoor latrine. On Day 3 I could stand long enough to shower. It’s a horrible disease, and I was lucky.

Humanitarian nurses need to understand this important and widespread disease. We won’t always have a doctor to prescribe, and the nurse may be the primary care provider. We need to be able to recognize the symptoms, diagnose and appropriately treat ourselves and our patients … sometimes just one, sometimes hundreds. And we need to be vigilant in prevention. DEET and nets are our best friends.

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